EFFECT OF INSULIN AND AMINO ACIDS ON STRESS INDUCED PROTEOLYSIS

伴随着严重损伤或创伤的皮质类固醇过量会导致肌肉蛋白质加速分解。蛋白分解的增加尤其具有威胁性，因为它会导致肌肉萎缩和虚弱。高皮质醇血症的特征是肌肉蛋白质分解增加，而蛋白质合成减少或保持不变。动物模型和间接人体数据的证据表明，肌肉氨基酸的摄取受到损害。因此，我们将探讨蛋白质分解在调节肌肉蛋白质代谢变化中的中心作用的假设。我们将确定急性(8小时)和皮质醇治疗4天(6 mg/m~2/小时)对氨基酸跨膜转运的影响。我们随后将确定合成代谢因子(胰岛素和氨基酸)在皮质醇过量时对氨基酸运输和肌肉蛋白质代谢的影响。稳定的同位素示踪剂将被用来测量正常志愿者的这些影响。

Corticosteriod excess that accompanies major injury or trauma results in an accelerated muscle protein breakdown. The increased proteolysis is especially threatening as it results in muscle wasting and debility. Hypercortisolemia is characterized by an increase in muscle protein breakdown, while protein synthesis decreases or remains unchanged. Evidence in animal models and indirect human data suggest that muscle amino acid uptake is impaired. Therefore, we will investigate the hypothesis protein breakdown is central in mediating changes in muscle protein metabolism. We will determine the effect of acute (8hr) and four days of cortisol treatment (6 mg/m2/hr) on transmembrane amino acid transport. We will subsequently determine the effect of anabolic factors (insulin and amino acid) on amino acid transport and muscle protein metabolism during cortisol excess. Stable isotope tracers will be utilized to measure these effects in normal volunteers.